Dokument

Zusammenfassung:
Neuronal preconditioning describes a phenomenon that affords robust brain tolerance against neurodegenerative insults. This adaptive cytoprotection is a fundamental capability of living cells, allowing them to survive exposure to potentially recurrent stressors. The research of the molecular and cellular signaling during this self-protecting process is an important tool to develop novel strategies for the treatment of diseases that are characterized by neuronal cell death, which causes progressive loss of brain tissue and function after acute brain injury and in chronic neurodegenerative diseases. The major aim of this study was to investigate preconditioning effects in a model of neuronal cell death on the molecular and cellular level. This issue was addressed in immortalized mouse hippocampal HT-22 neurons exposed to glutamate toxicity, which selectively induces oxidative stress through glutathione depletion. The first part of the present study investigates, whether the neuroprotective effect mediated by the depletion of the pro-apoptotic protein AIF is attributed to mitochondrial preconditioning. AIF is a mitochondrial protein that mediates caspase-independent cell death after translocation into the nucleus by chromatin condensation and large-scale DNA fragmentation. The findings of this study demonstrate that AIF gene silencing protects mitochondrial function and integrity in a paradigm of lethal oxidative stress in the used neural cell line. Depletion of AIF preserved mitochondrial morphology, mitochondrial membrane potential, and ATP levels after induction of oxidative stress in HT-22 cells, and this mitoprotective effect also significantly attenuated the secondary increase in lipid peroxidation which was associated with mitochondrial damage and cell death in this model system. Furthermore, AIF depletion was associated with reduced complex I expression levels, and similar to protective effects achieved by low doses of the complex I inhibitor rotenone. These results suggest for the first time that AIF silencing provides protection against oxidative cell death at the level of mitochondria by preconditioning and not at the level of apoptotic DNA damage in the nucleus. The second part of this thesis investigated conditioned medium (CM), which was generated by neural progenitor cells (NPCs) that undergo starvation-induced apoptosis after growth factor withdrawal. It is well established that transplantation of stem/progenitor cells to the brain improve abnormal motor behavior and memory function in a broad spectrum of neurodegenerative diseases and after acute brain injury. However, stem cell-based therapy still holds many risks and unresolved issues regarding the mode of action and the optimal application. The validation of a CM from dying NPCs reflects the conditions after stem/progenitor cell injection since only very few cells survive after the transplantation. The findings of the present study clearly demonstrate that CM provides very potent, long-lasting, and stable neuroprotective effects that can even be further increased by heat activation. The data also indicate that cell lysis is essential for the generation of protective properties. Thus, the release of neuroprotective substances during the cell death of stem/progenitor cells seems to be a kind of cellular communication that protects neighboring cells and other tissues. Interestingly, a variety of proteins were identified as potential candidates that mediated the neuroprotective effect of CM, such as prdx-1 and gal-1. Further, the contribution of a low molecular weight cofactor was found. Thus, the results of these investigations are the basis for the development of a highly potent, standardized composition for the therapy of neurodegenerative diseases and acute brain injury. In summary, the data from this thesis highlight the neuroprotective potential of preconditioning effects for the regulation of cell survival after neurodegenerative insults. In addition, they indicate the importance of understanding the underlying mechanisms to develop new strategies for the therapy of neurodegenerative diseases.

Bibliographie / References

1. Bang, O. Y., J. S. Lee, P. H. Lee, and G. Lee, 2005, Autologous mesenchymal stem cell transplantation in stroke patients: Ann.Neurol., v. 57, no. 6, p. 874-882.
2. Yang, H. Y. et al., 2008a, Gene expression profiling related to the enhanced erythropoiesis in mouse bone marrow cells: J.Cell Biochem., v. 104, no. 1, p. 295-303.
3. Yamane, J. et al., 2010, Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets: J.Neurosci.Res., v. 88, no. 7, p. 1394-1405.
4. Cho, Y. J. et al., 2012, Therapeutic effects of human adipose stem cell-conditioned medium on stroke: J.Neurosci.Res., v. 90, no. 9, p. 1794-1802.
5. Hattori, F., and S. Oikawa, 2007, Peroxiredoxins in the central nervous system: Subcell.Biochem., v. 44, p. 357-374.
6. Walker, J. M., 1994, The bicinchoninic acid (BCA) assay for protein quantitation: Methods Mol.Biol., v. 32, p. 5-8.
7. Karray, A., Y. Gargouri, R. Verger, and S. Bezzine, 2012b, Phospholipase A2 purification and characterization: a case study: Methods Mol.Biol., v. 861, p. 283-297.
8. Lin, S. L., and S. Y. Ying, 2013, Mechanism and Method for Generating Tumor-Free iPS Cells Using Intronic MicroRNA miR-302 Induction: Methods Mol.Biol., v. 936, p. 295-312.
9. Burda, J. et al., 2006, Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain: Cell Mol.Neurobiol., v. 26, no. 7-8, p. 1141-1151.
10. Scheibe, F., O. Klein, J. Klose, and J. Priller, 2012, Mesenchymal stromal cells rescue cortical neurons from apoptotic cell death in an in vitro model of cerebral ischemia: Cell Mol.Neurobiol., v. 32, no. 4, p. 567-576.
11. Qu, W. S., Y. H. Wang, J. P. Wang, Y. X. Tang, Q. Zhang, D. S. Tian, Z. Y. Yu, M. J. Xie, and W. Wang, 2010, Galectin-1 enhances astrocytic BDNF production and improves functional outcome in rats following ischemia: Neurochem.Res., v. 35, no. 11, p. 1716-1724.
12. Cadet, J. L., and I. N. Krasnova, 2009, Cellular and molecular neurobiology of brain preconditioning: Mol.Neurobiol., v. 39, no. 1, p. 50-61.
13. Busija, D. W., T. Gaspar, F. Domoki, P. V. Katakam, and F. Bari, 2008, Mitochondrial- mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning: Adv.Drug Deliv.Rev., v. 60, no. 13-14, p. 1471-1477.
14. Karray, A., A. Y. Ben, J. Boujelben, S. Amara, F. Carriere, Y. Gargouri, and S. Bezzine, 2012a, Drastic changes in the tissue-specific expression of secreted phospholipases A2 in chicken pulmonary disease: Biochimie, v. 94, no. 2, p. 451-460.
15. Lebuffe, 2008, Preconditioning by an in situ administration of hydrogen peroxide: involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia-reperfusion model: Brain Res., v. 1240, p. 177-184.
16. Mehta, S. L., N. Manhas, and R. Raghubir, 2007, Molecular targets in cerebral ischemia for developing novel therapeutics: Brain Res.Rev., v. 54, no. 1, p. 34-66.
17. Sack, M. N., 2006, Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance: Cardiovasc.Res., v. 72, no. 2, p. 210-219.
18. Meco, M., S. Cirri, C. Gallazzi, G. Magnani, and D. Cosseta, 2007, Desflurane preconditioning in coronary artery bypass graft surgery: a double-blinded, randomised and placebo-controlled study: Eur.J.Cardiothorac.Surg., v. 32, no. 2, p. 319-325.
19. Chang-Hong, R. et al., 2005, Neuroprotective effect of oxidized galectin-1 in a transgenic mouse model of amyotrophic lateral sclerosis: Exp.Neurol., v. 194, no. 1, p. 203-211.
20. Hisatomi, T., T. Ishibashi, J. W. Miller, and G. Kroemer, 2009, Pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection: Exp.Neurol., v. 218, no. 2, p. 347-352.
21. Ray, J., and F. H. Gage, 2006, Differential properties of adult rat and mouse brain-derived neural stem/progenitor cells: Mol.Cell Neurosci., v. 31, no. 3, p. 560-573.
22. Sutton, M. A., A. M. Taylor, H. T. Ito, A. Pham, and E. M. Schuman, 2007, Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis: Neuron, v. 55, no. 4, p. 648-661.
23. Liebelt, B. et al., 2010, Exercise preconditioning reduces neuronal apoptosis in stroke by up- regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated- kinase 1/2: Neuroscience, v. 166, no. 4, p. 1091-1100.
24. Polazzi, E., and B. Monti, 2010, Microglia and neuroprotection: from in vitro studies to therapeutic applications: Prog.Neurobiol., v. 92, no. 3, p. 293-315.
25. Nakaso, K., H. Yano, Y. Fukuhara, T. Takeshima, K. Wada-Isoe, and K. Nakashima, 2003, PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells: FEBS Lett., v. 546, no. 2-3, p. 181-184.
26. Hashimoto, R., N. Takei, K. Shimazu, L. Christ, B. Lu, and D. M. Chuang, 2002, Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity: Neuropharmacology, v. 43, no. 7, p. 1173-1179.
27. Yang, R. Y., G. A. Rabinovich, and F. T. Liu, 2008b, Galectins: structure, function and therapeutic potential: Expert.Rev.Mol.Med., v. 10, p. e17.
28. Tretter, L., I. Sipos, and V. dam-Vizi, 2004, Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson's disease: Neurochem.Res., v. 29, no. 3, p. 569- 577.
29. Osato, K. et al., 2010, Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation: Cell Death.Dis., v. 1, p. e84.
30. Mack, G. S., 2011, ReNeuron and StemCells get green light for neural stem cell trials: Nat.Biotechnol., v. 29, no. 2, p. 95-97.
31. Shichita, T. et al., 2012, Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain: Nat.Med..
32. Prockop, D. J., 2012, Mitochondria to the rescue: Nat.Med., v. 18, no. 5, p. 653-654.
33. Gidday, J. M., 2006, Cerebral preconditioning and ischaemic tolerance: Nat.Rev.Neurosci., v.
34. Zhu, C. et al., 2007, Apoptosis-inducing factor is a major contributor to neuronal loss induced by neonatal cerebral hypoxia-ischemia: Cell Death.Differ., v. 14, no. 4, p. 775-784.
35. Simon, 2008, In vivo and in vitro characterization of a novel neuroprotective strategy for stroke: ischemic postconditioning: J.Cereb.Blood Flow Metab, v. 28, no. 2, p. 232-241.
36. Yu, S. W., Y. Wang, D. S. Frydenlund, O. P. Ottersen, V. L. Dawson, and T. M. Dawson, 2009, Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release: ASN.Neuro., v. 1, no. 5.
37. Guigas, B., N. Taleux, M. Foretz, D. Detaille, F. Andreelli, B. Viollet, and L. Hue, 2007, AMP- activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside: Biochem.J., v. 404, no. 3, p. 499-507.
38. Ravati, A., B. Ahlemeyer, A. Becker, S. Klumpp, and J. Krieglstein, 2001, Preconditioning- induced neuroprotection is mediated by reactive oxygen species and activation of the transcription factor nuclear factor-kappaB: J.Neurochem., v. 78, no. 4, p. 909-919.
39. Zhu, C., L. Qiu, X. Wang, U. Hallin, C. Cande, G. Kroemer, H. Hagberg, and K. Blomgren, 2003, Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain: J.Neurochem., v. 86, no. 2, p. 306-317.
40. Brown, D., B. D. Yu, N. Joza, P. Benit, J. Meneses, M. Firpo, P. Rustin, J. M. Penninger, and G. R. Martin, 2006, Loss of Aif function causes cell death in the mouse embryo, but the temporal progression of patterning is normal: Proc.Natl.Acad.Sci.U.S.A, v. 103, no. 26, p. 9918-9923.
41. Bajgar, R., S. Seetharaman, A. J. Kowaltowski, K. D. Garlid, and P. Paucek, 2001, Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain: J.Biol.Chem., v. 276, no. 36, p. 33369-33374.
42. Polster, B. M., G. Basanez, A. Etxebarria, J. M. Hardwick, and D. G. Nicholls, 2005, Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria: J.Biol.Chem., v. 280, no. 8, p. 6447-6454.
43. Wang, Y., D. L. Huso, J. Harrington, J. Kellner, D. K. Jeong, J. Turney, and I. K. McNiece, 2005, Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture: Cytotherapy., v. 7, no. 6, p. 509-519.
44. Cregan, S. P. et al., 2002, Apoptosis-inducing factor is involved in the regulation of caspase- independent neuronal cell death: J.Cell Biol., v. 158, no. 3, p. 507-517.
45. Kim-Han, J. S., and L. L. Dugan, 2005, Mitochondrial uncoupling proteins in the central nervous system: Antioxid.Redox.Signal., v. 7, no. 9-10, p. 1173-1181.
46. Gan, Y. et al., 2012, Transgenic overexpression of peroxiredoxin-2 attenuates ischemic neuronal injury via suppression of a redox-sensitive pro-death signaling pathway: Antioxid.Redox.Signal., v. 17, no. 5, p. 719-732.
47. Wiegand, F. et al., 1999, Respiratory chain inhibition induces tolerance to focal cerebral ischemia: J.Cereb.Blood Flow Metab, v. 19, no. 11, p. 1229-1237.
48. Masada, T., Y. Hua, G. Xi, S. R. Ennis, and R. F. Keep, 2001, Attenuation of ischemic brain edema and cerebrovascular injury after ischemic preconditioning in the rat: J.Cereb.Blood Flow Metab, v. 21, no. 1, p. 22-33.
49. Prass, K., K. Ruscher, M. Karsch, N. Isaev, D. Megow, J. Priller, A. Scharff, U. Dirnagl, and A. Meisel, 2002, Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro: J.Cereb.Blood Flow Metab, v. 22, no. 5, p. 520-525.
50. Plesnila, N., C. Zhu, C. Culmsee, M. Groger, M. A. Moskowitz, and K. Blomgren, 2004, Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia: J.Cereb.Blood Flow Metab, v. 24, no. 4, p. 458-466.
51. Nasrabady, S. E., A. Kuzhandaivel, and A. Nistri, 2011, Studies of locomotor network neuroprotection by the selective poly(ADP-ribose) polymerase-1 inhibitor PJ-34 against excitotoxic injury to the rat spinal cord in vitro: Eur.J.Neurosci., v. 33, no. 12, p. 2216-2227.
52. Gaspar, T., P. Katakam, J. A. Snipes, B. Kis, F. Domoki, F. Bari, and D. W. Busija, 2008, Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels: J.Neurochem., v. 105, no. 4, p. 1115-1128.
53. Ronnett, G. V., S. Ramamurthy, A. M. Kleman, L. E. Landree, and S. Aja, 2009, AMPK in the brain: its roles in energy balance and neuroprotection: J.Neurochem., v. 109 Suppl 1, p. 17- 23.
54. Correia, S. C., and P. I. Moreira, 2010, Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration?: J.Neurochem., v. 112, no. 1, p. 1-12.
55. Sakaguchi, M. et al., 2010, Regulation of adult neural progenitor cells by Galectin-1/beta1 Integrin interaction: J.Neurochem., v. 113, no. 6, p. 1516-1524.
56. Joza, N. et al., 2005, Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy: Mol.Cell Biol., v. 25, no. 23, p. 10261-10272.
57. Wakatsuki, and Z. J. Bosnjak, 2010, Mitochondrial depolarization underlies delay in permeability transition by preconditioning with isoflurane: roles of ROS and Ca2+: Am.J.Physiol Cell Physiol, v. 299, no. 2, p. C506-C515.
58. Kim, Y. J., J. Y. Ahn, P. Liang, C. Ip, Y. Zhang, and Y. M. Park, 2007, Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology: Cancer Res., v. 67, no. 2, p. 546-554.
59. Tulsawani, R., L. S. Kelly, N. Fatma, B. Chhunchha, E. Kubo, A. Kumar, and D. P. Singh, 2010, Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage: BMC.Neurosci., v. 11, p. 125.
60. Jackson, J. S., J. P. Golding, C. Chapon, W. A. Jones, and K. K. Bhakoo, 2010, Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study: Stem Cell Res.Ther., v. 1, no. 2, p. 17.
61. Kim, S. U. et al., 2008a, Peroxiredoxin I is an indicator of microglia activation and protects against hydrogen peroxide-mediated microglial death: Biol.Pharm.Bull., v. 31, no. 5, p. 820- 825.
62. Robinson, M. B., J. L. Tidwell, T. Gould, A. R. Taylor, J. M. Newbern, J. Graves, M. Tytell, and C. E. Milligan, 2005, Extracellular heat shock protein 70: a critical component for motoneuron survival: J.Neurosci., v. 25, no. 42, p. 9735-9745.
63. Lin, J. H. et al., 2008, A central role of connexin 43 in hypoxic preconditioning: J.Neurosci., v. 28, no. 3, p. 681-695.
64. Hu, X. et al., 2011, Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the apoptosis signal-regulating kinase (ASK1) signaling cascade: J.Neurosci., v. 31, no. 1, p. 247-261.
65. Tan, S., D. Schubert, and P. Maher, 2001, Oxytosis: A novel form of programmed cell death: Curr.Top.Med.Chem., v. 1, no. 6, p. 497-506.
66. Xie, Z., J. Zhang, J. Wu, B. Viollet, and M. H. Zou, 2008, Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes: Diabetes, v. 57, no. 12, p. 3222-3230.
67. Lehner, 2002, Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70: J.Immunol., v. 169, no. 5, p. 2422-2429.
68. Walker, P. A., P. A. Letourneau, S. Bedi, S. K. Shah, F. Jimenez, and C. S. Jr, 2011, Progenitor cells as remote "bioreactors": neuroprotection via modulation of the systemic inflammatory response: World J.Stem Cells, v. 3, no. 2, p. 9-18.
69. Zhu, J. M., Y. Y. Zhao, S. D. Chen, W. H. Zhang, L. Lou, and X. Jin, 2011, Functional recovery after transplantation of neural stem cells modified by brain-derived neurotrophic factor in rats with cerebral ischaemia: J.Int.Med.Res., v. 39, no. 2, p. 488-498.
70. Amariglio, N. et al., 2009, Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient: PLoS.Med., v. 6, no. 2, p. e1000029.
71. Öxler, E. M., A. Dolga, and C. Culmsee, 2012, AIF depletion provides neuroprotection through a preconditioning effect: Apoptosis..
72. Hara, 2008, A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di- oxopropyl)amino)carbonyl)-3-met hylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice: Neuroscience, v. 157, no. 2, p. 309-318.
73. (4-chlorophenyl)-1-piperazinyl] propyl]-4(3H)-quinazolinone (FR255595), in an in vitro References 157 model of cell death and in mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease: J.Pharmacol.Exp.Ther., v. 309, no. 3, p. 1067-1078.
74. Sakaguchi, M. et al., 2006, A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells: Proc.Natl.Acad.Sci.U.S.A, v. 103, no. 18, p. 7112-7117.
75. Ming, G. L., and H. Song, 2011, Adult neurogenesis in the mammalian brain: significant answers and significant questions: Neuron, v. 70, no. 4, p. 687-702.
76. Modjtahedi, N., F. Giordanetto, and G. Kroemer, 2010, A human mitochondriopathy caused by AIF mutation: Cell Death.Differ., v. 17, no. 10, p. 1525-1528.
77. Vahsen, N. et al., 2004, AIF deficiency compromises oxidative phosphorylation: EMBO J., v. 23, no. 23, p. 4679-4689.
78. Lee, J. S., J. M. Hong, G. J. Moon, P. H. Lee, Y. H. Ahn, and O. Y. Bang, 2010, A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke: Stem Cells, v. 28, no. 6, p. 1099-1106.
79. Janoff, A., 1964, Alterations in lysosomes (intracellular enzymes) during shock; effects of preconditioning (tolerance) and protective drugs: Int.Anesthesiol.Clin., v. 2, p. 251-269.
80. Kim, S. Y., T. J. Kim, and K. Y. Lee, 2008b, A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway: FEBS Lett., v. 582, no. 13, p. 1913-1918.
81. Kerr, J. F., A. H. Wyllie, and A. R. Currie, 1972, Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics: Br.J.Cancer, v. 26, no. 4, p. 239-257.
82. McIntosh, D. S. Park, S. A. Bennett, and R. S. Slack, 2005, Apoptosis-inducing factor is a References 153 key factor in neuronal cell death propagated by BAX-dependent and BAX-independent mechanisms: J.Neurosci., v. 25, no. 6, p. 1324-1334.
83. Mattson, M. P., 2000, Apoptosis in neurodegenerative disorders: Nat.Rev.Mol.Cell Biol., v. 1, no. 2, p. 120-129.
84. Hristov, M., W. Erl, S. Linder, and P. C. Weber, 2004, Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro: Blood, v. 104, no. 9, p. 2761-2766.
85. Li, F., Q. Huang, J. Chen, Y. Peng, D. R. Roop, J. S. Bedford, and C. Y. Li, 2010, Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration: Sci.Signal., v. 3, no. 110, p. ra13.
86. Geuskens, and G. Kroemer, 1996, Bcl-2 inhibits the mitochondrial release of an apoptogenic protease: J.Exp.Med., v. 184, no. 4, p. 1331-1341.
87. Landshamer, S. et al., 2008, Bid-induced release of AIF from mitochondria causes immediate neuronal cell death: Cell Death.Differ., v. 15, no. 10, p. 1553-1563.
88. Tobaben, S., J. Grohm, A. Seiler, M. Conrad, N. Plesnila, and C. Culmsee, 2011, Bid- mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons: Cell Death.Differ., v. 18, no. 2, p. 282-292.
89. Parr, A. M., C. H. Tator, and A. Keating, 2007, Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury: Bone Marrow Transplant., v. 40, no. 7, p. 609-619.
90. Culmsee, 2007, Bone marrow stromal cells mediate protection through stimulation of PI3- K/Akt and MAPK signaling in neurons: Neurochem.Int., v. 50, no. 1, p. 243-250.
91. Poser, S., S. Impey, Z. Xia, and D. R. Storm, 2003, Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP: J.Neurosci., v. 23, no. 11, p. 4420-4427.
92. Ratajczak, M. Z., 2005, Cancer stem cells--normal stem cells "Jedi" that went over to the "dark side": Folia Histochem.Cytobiol., v. 43, no. 4, p. 175-181.
93. Pellettieri, J., P. Fitzgerald, S. Watanabe, J. Mancuso, D. R. Green, and A. A. Sanchez, 2010, Cell death and tissue remodeling in planarian regeneration: Dev.Biol., v. 338, no. 1, p. 76-85.
94. Oppenheim, R. W., 1991, Cell death during development of the nervous system: Annu.Rev.Neurosci., v. 14, p. 453-501.
95. Vaux, D. L., and S. J. Korsmeyer, 1999, Cell death in development: Cell, v. 96, no. 2, p. 245- 254.
96. Sagara, Y., R. Dargusch, D. Chambers, J. Davis, D. Schubert, and P. Maher, 1998, Cellular mechanisms of resistance to chronic oxidative stress: Free Radic.Biol.Med., v. 24, no. 9, p. 1375-1389.
97. Marshall, J., 1994, Clinical developments in cerebrovascular disease: J.Hist Neurosci., v. 3, no. 2, p. 115-118.
98. Culmsee, C., V. Junker, W. Kremers, S. Thal, N. Plesnila, and J. Krieglstein, 2004, Combination therapy in ischemic stroke: synergistic neuroprotective effects of memantine and clenbuterol: Stroke, v. 35, no. 5, p. 1197-1202.
99. Vendrame, M., C. Gemma, K. R. Pennypacker, P. C. Bickford, S. C. Davis, P. R. Sanberg, and A. E. Willing, 2006, Cord blood rescues stroke-induced changes in splenocyte phenotype and function: Exp.Neurol., v. 199, no. 1, p. 191-200.
100. Choi, H. J., S. W. Kang, C. H. Yang, S. G. Rhee, and S. E. Ryu, 1998, Crystal structure of a novel human peroxidase enzyme at 2.0 A resolution: Nat.Struct.Biol., v. 5, no. 5, p. 400-406.
101. Smith-Pearson, P. S., M. Kooshki, D. R. Spitz, L. B. Poole, W. Zhao, and M. E. Robbins, 2008, Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2): Free Radic.Biol.Med., v. 45, no. 8, p. 1178-1189.
102. Zhang, L., Y. Li, C. Zhang, M. Chopp, A. Gosiewska, and K. Hong, 2011, Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia: Stroke, v. 42, no. 5, p. 1437-1444.
103. Yang, D. et al., 2011, Deletion of peroxiredoxin 6 potentiates lipopolysaccharide-induced acute lung injury in mice: Crit Care Med., v. 39, no. 4, p. 756-764.
104. Zernecke, A. et al., 2009, Delivery of microRNA-126 by apoptotic bodies induces CXCL12- dependent vascular protection: Sci.Signal., v. 2, no. 100, p. ra81.
105. Villarroya, and M. G. Lopez, 2006, Depolarization preconditioning produces cytoprotection against veratridine-induced chromaffin cell death: Eur.J.Pharmacol., v. 553, no. 1-3, p. 28-38.
106. Cheung, E. C. et al., 2006, Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis: EMBO J., v. 25, no. 17, p. 4061-4073.
107. Yuan, J., M. Lipinski, and A. Degterev, 2003, Diversity in the mechanisms of neuronal cell death: Neuron, v. 40, no. 2, p. 401-413.
108. Ye, H. et al., 2002, DNA binding is required for the apoptogenic action of apoptosis inducing factor: Nat.Struct.Biol., v. 9, no. 9, p. 680-684.
109. Kuhn, H. G., J. Winkler, G. Kempermann, L. J. Thal, and F. H. Gage, 1997, Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain: J.Neurosci., v. 17, no. 15, p. 5820-5829.
110. Neumann, C. A. et al., 2003, Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression: Nature, v. 424, no. 6948, p. 561-565.
111. Joza, N. et al., 2001, Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death: Nature, v. 410, no. 6828, p. 549-554.
112. Morimoto, B. H., and D. E. Koshland, Jr., 1990, Excitatory amino acid uptake and N-methyl- D-aspartate-mediated secretion in a neural cell line: Proc.Natl.Acad.Sci.U.S.A, v. 87, no. 9, p. 3518-3521.
113. Oppenheim, J. Caress, and C. E. Milligan, 2007, Exogenous delivery of heat shock protein 70 increases lifespan in a mouse model of amyotrophic lateral sclerosis: J.Neurosci., v. 27, no. 48, p. 13173-13180.
114. Otera, H., S. Ohsakaya, Z. Nagaura, N. Ishihara, and K. Mihara, 2005, Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space: EMBO J., v. 24, no. 7, p. 1375-1386.
115. Hong, and Y. L. Chen, 2008, Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells: Oncogene, v. 27, no. 26, p. 3746-3753.
116. Camby, I., M. M. Le, F. Lefranc, and R. Kiss, 2006, Galectin-1: a small protein with major functions: Glycobiology, v. 16, no. 11, p. 137R-157R.
117. Starossom, S. C. et al., 2012, Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration: Immunity., v. 37, no. 2, p. 249-263.
118. Horie, H. et al., 1999, Galectin-1 regulates initial axonal growth in peripheral nerves after axotomy: J.Neurosci., v. 19, no. 22, p. 9964-9974.
119. Barondes, S. H. et al., 1994, Galectins: a family of animal beta-galactoside-binding lectins: Cell, v. 76, no. 4, p. 597-598.
120. Mitrecic, D., C. Nicaise, L. Klimaschewski, S. Gajovic, D. Bohl, and R. Pochet, 2012, Genetically modified stem cells for the treatment of neurological diseases: Front Biosci.(Elite.Ed), v. 4, p. 1170-1181.
121. Gesuete, R., F. Orsini, E. R. Zanier, D. Albani, M. A. Deli, G. Bazzoni, and M. G. De Simoni, 2011, Glial cells drive preconditioning-induced blood-brain barrier protection: Stroke, v. 42, no. 5, p. 1445-1453.
122. Marin, P., K. L. Nastiuk, N. Daniel, J. A. Girault, A. J. Czernik, J. Glowinski, A. C. Nairn, and J. Premont, 1997, Glutamate-dependent phosphorylation of elongation factor-2 and inhibition of protein synthesis in neurons: J.Neurosci., v. 17, no. 10, p. 3445-3454.
123. Murphy, T. H., M. Miyamoto, A. Sastre, R. L. Schnaar, and J. T. Coyle, 1989, Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress: Neuron, v. 2, no. 6, p. 1547-1558.
124. Tytell, M., S. G. Greenberg, and R. J. Lasek, 1986, Heat shock-like protein is transferred from glia to axon: Brain Res., v. 363, no. 1, p. 161-164.
125. Huang, C., H. Cheng, S. Hao, H. Zhou, X. Zhang, J. Gao, Q. H. Sun, H. Hu, and C. C. Wang, 2006, Heat shock protein 70 inhibits alpha-synuclein fibril formation via interactions with diverse intermediates: J.Mol.Biol., v. 364, no. 3, p. 323-336.
126. Brown, I. R., 2007, Heat shock proteins and protection of the nervous system: Ann.N.Y.Acad.Sci., v. 1113, p. 147-158.
127. Romi, F., G. Helgeland, and N. E. Gilhus, 2011, Heat-shock proteins in clinical neurology: Eur.Neurol., v. 66, no. 2, p. 65-69.
128. Banerjee, S., D. Williamson, N. Habib, M. Gordon, and J. Chataway, 2011, Human stem cell therapy in ischaemic stroke: a review: Age Ageing, v. 40, no. 1, p. 7-13.
129. Chung, and P. R. Sanberg, 2009, Human umbilical cord blood cell grafts for brain ischemia: Cell Transplant., v. 18, no. 9, p. 985-998.
130. Jäderstad, J., H. Brismar, and E. Herlenius, 2010, Hypoxic preconditioning increases gap- junctional graft and host communication: Neuroreport, v. 21, no. 17, p. 1126-1132.
131. Seo, M. S., S. W. Kang, K. Kim, I. C. Baines, T. H. Lee, and S. G. Rhee, 2000, Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate: J.Biol.Chem., v. 275, no. 27, p. 20346-20354.
132. Ludolph, U. Dirnagl, and J. Hugon, 1997a, Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning": J.Cereb.Blood Flow Metab, v. 17, no. 3, p. 257-264.
133. Ben-Shachar, 2012, Induced pluripotent stem cells from hair follicles as a cellular model for neurodevelopmental disorders: Stem Cell Res., v. 8, no. 1, p. 134-140.
134. Takahashi, K., and S. Yamanaka, 2006, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors: Cell, v. 126, no. 4, p. 663-676.
135. Sanberg, P. R. Sanberg, and A. E. Willing, 2004, Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume: Stroke, v. 35, no. 10, p. 2390-2395.
136. Lledo, P. M., and A. Saghatelyan, 2005, Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience: Trends Neurosci., v. 28, no. 5, p. 248-254.
137. Chopp, 2002, Ischemic rat brain extracts induce human marrow stromal cell growth factor production: Neuropathology., v. 22, no. 4, p. 275-279.
138. Kirino, T., 2002, Ischemic tolerance: J.Cereb.Blood Flow Metab, v. 22, no. 11, p. 1283-1296.
139. Gage, F. H., 2000, Mammalian neural stem cells: Science, v. 287, no. 5457, p. 1433-1438.
140. Li, Y., and M. Chopp, 2009, Marrow stromal cell transplantation in stroke and traumatic brain injury: Neurosci.Lett., v. 456, no. 3, p. 120-123.
141. Liu, Y., D. A. Peterson, H. Kimura, and D. Schubert, 1997, Mechanism of cellular 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction: J.Neurochem., v. 69, no. 2, p. 581-593.
142. Zhao, C., W. Deng, and F. H. Gage, 2008, Mechanisms and functional implications of adult neurogenesis: Cell, v. 132, no. 4, p. 645-660.
143. Yakovlev, A. G., and A. I. Faden, 2004, Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies: NeuroRx., v. 1, no. 1, p. 5-16.
144. M. Dawson, and V. L. Dawson, 2002, Mediation of poly(ADP-ribose) polymerase-1- dependent cell death by apoptosis-inducing factor: Science, v. 297, no. 5579, p. 259-263. References 167
145. Silva, G. V. et al., 2005, Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model: Circulation, v. 111, no. 2, p. 150-156.
146. Kakimura, J. et al., 2002, Microglial activation and amyloid-beta clearance induced by exogenous heat-shock proteins: FASEB J., v. 16, no. 6, p. 601-603.
147. Chan, P. H., 2004, Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia: Neurochem.Res., v. 29, no. 11, p. 1943-1949.
148. Lin, M. T., and M. F. Beal, 2006, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases: Nature, v. 443, no. 7113, p. 787-795.
149. Galluzzi, L., K. Blomgren, and G. Kroemer, 2009, Mitochondrial membrane permeabilization in neuronal injury: Nat.Rev.Neurosci., v. 10, no. 7, p. 481-494.
150. Zhang, D. X., and D. D. Gutterman, 2007, Mitochondrial reactive oxygen species-mediated signaling in endothelial cells: Am.J.Physiol Heart Circ.Physiol, v. 292, no. 5, p. H2023- H2031.
151. Correia, S. C., R. X. Santos, G. Perry, X. Zhu, P. I. Moreira, and M. A. Smith, 2010, Mitochondria: the missing link between preconditioning and neuroprotection: J.Alzheimers.Dis., v. 20 Suppl 2, p. S475-S485.
152. Chen, H., S. A. Detmer, A. J. Ewald, E. E. Griffin, S. E. Fraser, and D. C. Chan, 2003, Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development: J.Cell Biol., v. 160, no. 2, p. 189-200.
153. Susin, S. A. et al., 1999, Molecular characterization of mitochondrial apoptosis-inducing factor: Nature, v. 397, no. 6718, p. 441-446.
154. Galluzzi, L. et al., 2012, Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012: Cell Death.Differ., v. 19, no. 1, p. 107-120.
155. Williams, R. L. et al., 1988, Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells: Nature, v. 336, no. 6200, p. 684-687.
156. Madhavan, L., V. Ourednik, and J. Ourednik, 2008, Neural stem/progenitor cells initiate the formation of cellular networks that provide neuroprotection by growth factor-modulated antioxidant expression: Stem Cells, v. 26, no. 1, p. 254-265.
157. Lim, H. C. et al., 2008, Neuroprotective effect of neural stem cell-conditioned media in in vitro model of Huntington's disease: Neurosci.Lett., v. 435, no. 3, p. 175-180.
158. Chopp, 2007, One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke: Stroke, v. 38, no. 7, p. 2150-2156.
159. Lang, A. E., and A. M. Lozano, 1998a, Parkinson's disease. First of two parts: N.Engl.J.Med., v. 339, no. 15, p. 1044-1053.
160. Lang, A. E., and A. M. Lozano, 1998b, Parkinson's disease. Second of two parts: N.Engl.J.Med., v. 339, no. 16, p. 1130-1143.
161. Ferrara, N., and W. J. Henzel, 1989, Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells: Biochem.Biophys.Res.Commun., v. 161, no. 2, p. 851-858.
162. Dawson, and T. M. Dawson, 2011, Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos): Sci.Signal., v. 4, no. 167, p. ra20.
163. Staat, P. et al., 2005, Postconditioning the human heart: Circulation, v. 112, no. 14, p. 2143- 2148.
164. Venna, V. R., J. Li, S. E. Benashski, S. Tarabishy, and L. D. McCullough, 2012, Preconditioning induces sustained neuroprotection by downregulation of adenosine 5'- monophosphate-activated protein kinase: Neuroscience, v. 201, p. 280-287.
165. Xu, J., 2005, Preparation, culture, and immortalization of mouse embryonic fibroblasts: Curr.Protoc.Mol.Biol., v. Chapter 28, p. Unit.
166. Chinta, S. J., A. Rane, N. Yadava, J. K. Andersen, D. G. Nicholls, and B. M. Polster, 2009, Reactive oxygen species regulation by AIF-and complex I-depleted brain mitochondria: Free Radic.Biol.Med., v. 46, no. 7, p. 939-947.
167. Plaisant, F., A. Clippe, S. D. Vander, B. Knoops, and P. Gressens, 2003, Recombinant peroxiredoxin 5 protects against excitotoxic brain lesions in newborn mice: Free Radic.Biol.Med., v. 34, no. 7, p. 862-872.
168. Schägger, H., 2001, Respiratory chain supercomplexes: IUBMB.Life, v. 52, no. 3-5, p. 119- 128.
169. Zhou, G. et al., 2001, Role of AMP-activated protein kinase in mechanism of metformin action: J.Clin.Invest., v. 108, p. 346-356.
170. Zhao, Q., B. Lu, S. K. George, J. J. Yoo, and A. Atala, 2012, Safeguarding pluripotent stem cells for cell therapy with a non-viral, non-integrating episomal suicide construct: Biomaterials, v. 33, no. 29, p. 7261-7271.
171. Gallagher, G., and D. L. Forrest, 2007, Second solid cancers after allogeneic hematopoietic stem cell transplantation: Cancer, v. 109, no. 1, p. 84-92.
172. Chen, S., L. Yao, and T. J. Cunningham, 2012, Secreted phospholipase A2 involvement in neurodegeneration: differential testing of prosurvival and anti-inflammatory effects of enzyme inhibition: PLoS.One., v. 7, no. 6, p. e39257.
173. Hightower, L. E., and P. T. Guidon, Jr., 1989, Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins: J.Cell Physiol, v. 138, no. 2, p. 257-266.
174. Thomas, K. R., and M. R. Capecchi, 1987, Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells: Cell, v. 51, no. 3, p. 503-512.
175. Chmielewski, and M. D. Linnik, 1998, Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats: Stroke, v. 29, no. 1, p. 152-158.
176. Temple, S., 2001a, Stem cell plasticity--building the brain of our dreams: Nat.Rev.Neurosci., v. 2, no. 7, p. 513-520.
177. Lindvall, O., and Z. Kokaia, 2011, Stem cell research in stroke: how far from the clinic?: Stroke, v. 42, no. 8, p. 2369-2375.
178. Lindvall, O., and Z. Kokaia, 2006, Stem cells for the treatment of neurological disorders: Nature, v. 441, no. 7097, p. 1094-1096.
179. Wood, Z. A., E. Schroder, H. J. Robin, and L. B. Poole, 2003, Structure, mechanism and regulation of peroxiredoxins: Trends Biochem.Sci., v. 28, no. 1, p. 32-40.
180. Funatomi, H., and Y. Hatta, 1991, [Studies on heat stability of phospholipase A2 in human serum]: Nihon Shokakibyo Gakkai Zasshi, v. 88, no. 1, p. 71-76.
181. Verpelli, C., G. Piccoli, A. Zanchi, F. Gardoni, K. Huang, D. Brambilla, L. M. Di, E. Battaglioli, and C. Sala, 2010, Synaptic activity controls dendritic spine morphology by modulating eEF2-dependent BDNF synthesis: J.Neurosci., v. 30, no. 17, p. 5830-5842.
182. Pospisilik, J. A. et al., 2007, Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes: Cell, v. 131, no. 3, p. 476-491.
183. Götz, M., and W. B. Huttner, 2005, The cell biology of neurogenesis: Nat.Rev.Mol.Cell Biol., v. 6, no. 10, p. 777-788.
184. Temple, S., 2001b, The development of neural stem cells: Nature, v. 414, no. 6859, p. 112- 117.
185. Noble, R. L., 1943, The development of resistance by rats and guinea pigs to amount of trauma usually fatal: Am.J.Physiol., v. 138, p. 346-356.
186. Wang, W. X., B. W. Rajeev, A. J. Stromberg, N. Ren, G. Tang, Q. Huang, I. Rigoutsos, and P. T. Nelson, 2008, The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1: J.Neurosci., v. 28, no. 5, p. 1213-1223.
187. Klein, J. A., C. M. Longo-Guess, M. P. Rossmann, K. L. Seburn, R. E. Hurd, W. N. Frankel, R. T. Bronson, and S. L. Ackerman, 2002, The harlequin mouse mutation downregulates apoptosis-inducing factor: Nature, v. 419, no. 6905, p. 367-374.
188. Sasikumar, A. N., W. B. Perez, and T. G. Kinzy, 2012, The many roles of the eukaryotic elongation factor 1 complex: Wiley.Interdiscip.Rev.RNA., v. 3, no. 4, p. 543-555.
189. Kis, B., K. Nagy, J. A. Snipes, N. C. Rajapakse, T. Horiguchi, G. J. Grover, and D. W. Busija, 2004, The mitochondrial K(ATP) channel opener BMS-191095 induces neuronal preconditioning: Neuroreport, v. 15, no. 2, p. 345-349.
190. Kilic, E., U. Kilic, Y. Wang, C. L. Bassetti, H. H. Marti, and D. M. Hermann, 2006, The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia: FASEB J., v. 20, no. 8, p. 1185-1187.
191. Chen, J., Y. Li, L. Wang, Z. Zhang, D. Lu, M. Lu, and M. Chopp, 2001, Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats: Stroke, v. 32, no. 4, p. 1005-1011.
192. Onda, T., O. Honmou, K. Harada, K. Houkin, H. Hamada, and J. D. Kocsis, 2008, Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia: J.Cereb.Blood Flow Metab, v. 28, no. 2, p. 329-340.
193. Horie, N. et al., 2011, Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair: Stem Cells, v. 29, no. 2, p. 274-285.
194. Uzun, G., D. Subhani, and S. Amor, 2010, Trophic factors and stem cells for promoting recovery in stroke: J.Vasc.Interv.Neurol., v. 3, no. 1, p. 3-12.
195. Lindvall, O., Z. Kokaia, and A. Martinez-Serrano, 2004, Stem cell therapy for human neurodegenerative disorders-how to make it work: Nat.Med., v. 10 Suppl, p. S42-S50.
196. Weisova, P., D. Davila, L. P. Tuffy, M. W. Ward, C. G. Concannon, and J. H. Prehn, 2011, Role of 5'-adenosine monophosphate-activated protein kinase in cell survival and death responses in neurons: Antioxid.Redox.Signal., v. 14, no. 10, p. 1863-1876.
197. Puche, A. C., and B. Key, 1995, Identification of cells expressing galectin-1, a galactose- binding receptor, in the rat olfactory system: J.Comp Neurol., v. 357, no. 4, p. 513-523.
198. Nagy, K., B. Kis, N. C. Rajapakse, F. Bari, and D. W. Busija, 2004, Diazoxide preconditioning protects against neuronal cell death by attenuation of oxidative stress upon glutamate stimulation: J.Neurosci.Res., v. 76, no. 5, p. 697-704.
199. Kim, S. U., and J. de Vellis, 2009, Stem cell-based cell therapy in neurological diseases: a review: J.Neurosci.Res., v. 87, no. 10, p. 2183-2200.
200. Lekishvili, T., S. Hesketh, M. W. Brazier, and D. R. Brown, 2006, Mouse galectin-1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression: Eur.J.Neurosci., v. 24, no. 11, p. 3017-3025.
201. Sun, K. H., P. Y. de, F. Vincent, and K. Shah, 2008, Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction: J.Neurochem., v. 107, no. 1, p. 265-278.
202. Farooqui, A. A., W. Y. Ong, and L. A. Horrocks, 2006, Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders: Pharmacol.Rev., v. 58, no. 3, p. 591-620.
203. Riepe, M. W., K. Kasischke, and A. Raupach, 1997b, Acetylsalicylic acid increases tolerance against hypoxic and chemical hypoxia: Stroke, v. 28, no. 10, p. 2006-2011.
204. Liu, J., P. Narasimhan, F. Yu, and P. H. Chan, 2005, Neuroprotection by hypoxic preconditioning involves oxidative stress-mediated expression of hypoxia-inducible factor and erythropoietin: Stroke, v. 36, no. 6, p. 1264-1269.
205. Menasche, P., 2005, Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives: Thromb.Haemost., v. 94, no. 4, p. 697-701.
206. Montague, J. W., M. L. Gaido, C. Frye, and J. A. Cidlowski, 1994, A calcium-dependent nuclease from apoptotic rat thymocytes is homologous with cyclophilin. Recombinant cyclophilins A, B, and C have nuclease activity: J.Biol.Chem., v. 269, no. 29, p. 18877- 18880.
207. Mattiasson, G. et al., 2003, Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma: Nat.Med., v. 9, no. 8, p. 1062-1068.
208. Cande, C. et al., 2004, AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis: Oncogene, v. 23, no. 8, p. 1514-1521.
209. Majno, G., and I. Joris, 1995, Apoptosis, oncosis, and necrosis. An overview of cell death: Am.J.Pathol., v. 146, no. 1, p. 3-15.
210. Tan, S., Y. Sagara, Y. Liu, P. Maher, and D. Schubert, 1998, The regulation of reactive oxygen species production during programmed cell death: J.Cell Biol., v. 141, no. 6, p. 1423- 1432.
211. Slemmer, J. E. et al., 2008, Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury: Am.J.Pathol., v. 173, no. 6, p. 1795-1805.
212. Wang, Y., V. L. Dawson, and T. M. Dawson, 2009, Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos: Exp.Neurol., v. 218, no. 2, p. 193-202.
213. Wallace, D. C., 2005, A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine: Annu.Rev.Genet., v. 39, p. 359-407.
214. Mu, Y., S. W. Lee, and F. H. Gage, 2010, Signaling in adult neurogenesis: Curr.Opin.Neurobiol., v. 20, no. 4, p. 416-423.
215. Carletti, B., F. Piemonte, and F. Rossi, 2011, Neuroprotection: the emerging concept of restorative neural stem cell biology for the treatment of neurodegenerative diseases: Curr.Neuropharmacol., v. 9, no. 2, p. 313-317.
216. Margulis, 2001, In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance: Brain Res., v. 914, no. 1-2, p. 66-73.
217. Tang, X. Q., J. Q. Feng, J. Chen, P. X. Chen, J. L. Zhi, Y. Cui, R. X. Guo, and H. M. Yu, 2005, Protection of oxidative preconditioning against apoptosis induced by H2O2 in PC12 cells: mechanisms via MMP, ROS, and Bcl-2: Brain Res., v. 1057, no. 1-2, p. 57-64.
218. Hua, F., J. Ma, T. Ha, J. Kelley, D. L. Williams, R. L. Kao, J. H. Kalbfleisch, I. W. Browder, and C. Li, 2008, Preconditioning with a TLR2 specific ligand increases resistance to cerebral ischemia/reperfusion injury: J.Neuroimmunol., v. 199, no. 1-2, p. 75-82.
219. Grohm, J., N. Plesnila, and C. Culmsee, 2010, Bid mediates fission, membrane permeabilization and peri-nuclear accumulation of mitochondria as a prerequisite for oxidative neuronal cell death: Brain Behav.Immun., v. 24, no. 5, p. 831-838.
220. Lledo, P. M., M. Alonso, and M. S. Grubb, 2006, Adult neurogenesis and functional plasticity in neuronal circuits: Nat.Rev.Neurosci., v. 7, no. 3, p. 179-193.

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